Nuclear receptor profiling and screening services
transcriptional and biochemical assays
Orphagen is an industry leader in orphan nuclear receptor translational research. We have developed and validated transcriptional and biochemical assays for a panel of nuclear receptors. We provide flexible nuclear receptor profiling and screening services.
Compounds can be screened against single or multiple receptors in single or multiple doses for selectivity profiling and/or IC50 determination. Library screening service is available upon request. We are experienced in drug discovery and we meet the highest industry standards.
We perform validated assays for the following receptors:
• Metabolic receptors (FXR, LXRα,β; PPARα,δ,γ; and ERR α,β,γ)
• The steroid hormone receptors (ER, AR, PR, VDR, and GR)
• Retinoid receptors (RARα,β,γ and RXRα)
• Orphan targets (RORα and LRH-1)
• Custom receptor assay development upon request
| Receptor (human, mouse) | Cell Based Agonist Assay (1) | Cell Based Antagonist Assay (1) | FRET Based Biochemical Assay (2) |
| Metabolic Receptors | |||
| FXR (h) | X | X | |
| LXRα (m) | X | X | |
| LXRβ (h) | X | X | |
| PPARα (h) | X | X | |
| PPARδ (h) | X | X | |
| PPARγ (h) | X | X | |
| ERRα (h,m) | X | X | |
| ERRβ (h,m) | X | X | X |
| ERRγ (h,m) | X | X | X |
| Steroid Hormone Receptors | |||
| ERα (h) | X | ||
| AR (h) | X | X | |
| PR (h) | X | X | |
| VDR (h) | X | X | |
| GR (m) | X | X | |
| Retinoid Receptors | |||
| RARα (h) | X | X | |
| RARβ (h) | X | X | |
| RARγ (h) | X | X | |
| RXRα (h) | X | X | |
| Orphan Targets | |||
| RORα (h) | (3) | X | X |
| LRH-1 (h) | (3) | X | |
(1) A biochemical assay monitors receptor recruitment of a short peptide derived from an appropriate co-activator protein.
(2) The cell-based agonist and antagonist assays are based on transcription from a luciferase reporter by a Gal4 hybrid with the nuclear receptor ligand-binding domain.
(3) RORα and LRH-1 have high basal transcriptional activity. Antagonists can be characterized in the absence of agonist.
Flexible Screening & Profiling Options
We conduct high quality assays with fast turnaround time.
| Assays | Common Format | Customized Format | Turnaround Time |
| Cell Based Assay up to 8 receptors | Single dose or 10-point 2.5-fold dilution | Yes | 3 weeks |
| Nuclear Receptor Full Panel | Single dose or 10-point 2.5-fold dilution | Yes | 6 weeks |
Assay Performance and Data Reporting
For each receptor, assay Z-value and performance of standard agonist or antagonist are monitored to confirm assay performance1,2. Relative efficacy and IC50 of test compounds are reported together with raw data in an Excel file. Secure web-based data sharing is available upon request.
Contact us at info@orphagen.com or (858) 481-6191 for a quote.
References
- Madoux F, Li X, Chase P, Zastrow G, Cameron MD, Conkright JJ, Griffin PR, Thacher S, Hodder P: Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-throughput screening. Mol Pharmacol 73:1776-84, 2008
- Zhang JH, Chung TD, Oldenburg KR: A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen 4:67-73, 1999